A Small Animal Imaging Research program is proposed at U. Penn. (Penn-SAIR) supporting cancer research at Penn, the Wistar Institute, the Children's Hospital of Philadelphia (CHOP), the Lankenau Institute for Medical Research and Thomas Jefferson University;it will be available to other institutions within the Philadelphia region and world-wide. The program builds on a fully self-supported existing Small Animal Research Facility (SAIF). The SAIF, which came into existence with the termination of funding for the SAIRP and Pre-ICMIC programs, serves the needs of Penn as well as the cooperating institutions. It is supported by the Department of Radiology and the Comprehensive Cancer Center, of which it is a core. A complete administrative structure including an Oversight Committee, a Steering Committee, User Committee and an Animal Oversight Committee is already functioning. A Scientific Oversight Committee and Internal and External Advisory Boards would be added to supervise the base projects and imaging technology programs of the proposed SAIR. The SAIR will serve 4 NIH/DOD funded cancer oriented base projects in years 02-05: 1) Optical and PET imaging of therapeutic response in the hypoxic tumor microenvironment, Wafik S. El-Deiry, MD, PhD, PI;2) Orthotopic growth and therapy of human melanoma stem cells, Meenhard Herlyn, DVM, PhD, PI, Wistar;3) Development of PET and optical imaging probes for predicting therapeutic response of non-Hodgkin's lymphoma, Jerry D. Glickson, PhD, PI;4) Non-invasive imaging of breast cancer progression in inducible transgenic mouse models, Lewis A. Chodosh, MD, PhD, PI;and 4 more projects in years 03-05: 5) Transgenic mice as models for anti-vascular therapy, William M. Lee, MD, PhD, PI;6) Cancer cell adaptation to metabolic stress, Craig Thompson, MD, PhD, PI;7) Development of multifunctional nanoparticles for targeting therapeutic DNA delivery and visualization of ovarian metastatic tumors, Janet Sawicki, PhD, PI, Lankenau;and 8) Neuroblastoma biology and therapy: antiangiogenic strategies, John Maris, MD, PhD, PI, CHOP. The SAIR will support core facilities for NMR (MRI, MRS, and perfused cells), Nuclear Medicine (mPET, mSPECT, mCT), Optical Imaging, Bioluminescence, and Ultrasound with ancillary facilities for Radiochemistry, Chemistry, Molecular Biology, Image Analysis and Animal Tumor Models. Imaging technology developmental programs are proposed in NMR (DCE MRI, lactate/choline imaging, hyperpolarized 13C probes), PET(combined ?PET/MR/Optical imager), Optical Imaging (tomographic NIR imaging of tumor hypoxia by phosphorescence lifetime measurement), Radiochemistry (development of [18F] ethanolamine as a phospholipid metabolism probe), Chemistry (lipoprotein based iron oxide delivery system, GLUT1 targeted Gd-chelates, NIR molecular beacons for detecting specific phospholipases), and Molecular Biology (peptide nucleic acid based molecular beacons targeting the BRAF V600D,E mutation). A training program for physicians, graduate students, postdocs and technicians is proposed.